Figure 3

Hypothetical model for the evolution of T cell immunity over the human lifespan. Age-associated changes to T cell immunity result in decreasing proportions of naïve cells and increasing proportions of memory cells over the lifespan. TCR repertoire diversity is well-maintained at least until the end of the reproductive period, when repertoire shrinkage occurs rapidly. This point is reached as the number of different clonal expansions caused by persistent pathogens, as demonstrated for CMV, plateaus and then decreases. Loss of repertoire diversity in memory cells is not paralleled by their decreased numbers; on the contrary, these continue to rise as dysfunctional cells accumulate, possibly a compensatory mechanism. At this time also, responses to vaccination, as documented with influenza vaccination, are much less effective than at earlier time points.